Tripodi Marco, Evers Jan Felix, Mauss Alex, Bate Michael, Landgraf Matthias
Department of Zoology, University of Cambridge, Cambridge, United Kingdom.
PLoS Biol. 2008 Oct 28;6(10):e260. doi: 10.1371/journal.pbio.0060260.
As the nervous system develops, there is an inherent variability in the connections formed between differentiating neurons. Despite this variability, neural circuits form that are functional and remarkably robust. One way in which neurons deal with variability in their inputs is through compensatory, homeostatic changes in their electrical properties. Here, we show that neurons also make compensatory adjustments to their structure. We analysed the development of dendrites on an identified central neuron (aCC) in the late Drosophila embryo at the stage when it receives its first connections and first becomes electrically active. At the same time, we charted the distribution of presynaptic sites on the developing postsynaptic arbor. Genetic manipulations of the presynaptic partners demonstrate that the postsynaptic dendritic arbor adjusts its growth to compensate for changes in the activity and density of synaptic sites. Blocking the synthesis or evoked release of presynaptic neurotransmitter results in greater dendritic extension. Conversely, an increase in the density of presynaptic release sites induces a reduction in the extent of the dendritic arbor. These growth adjustments occur locally in the arbor and are the result of the promotion or inhibition of growth of neurites in the proximity of presynaptic sites. We provide evidence that suggest a role for the postsynaptic activity state of protein kinase A in mediating this structural adjustment, which modifies dendritic growth in response to synaptic activity. These findings suggest that the dendritic arbor, at least during early stages of connectivity, behaves as a homeostatic device that adjusts its size and geometry to the level and the distribution of input received. The growing arbor thus counterbalances naturally occurring variations in synaptic density and activity so as to ensure that an appropriate level of input is achieved.
随着神经系统的发育，分化中的神经元之间形成的连接存在内在变异性。尽管存在这种变异性，但仍形成了功能正常且非常稳健的神经回路。神经元处理其输入变异性的一种方式是通过其电特性的补偿性、稳态变化。在这里，我们表明神经元也会对其结构进行补偿性调整。我们分析了果蝇晚期胚胎中一个已识别的中枢神经元（aCC）在其首次建立连接并首次变得电活跃阶段的树突发育情况。同时，我们绘制了发育中的突触后树突上突触前位点的分布。对突触前伙伴进行基因操作表明，突触后树突会调整其生长以补偿突触位点活性和密度的变化。阻断突触前神经递质的合成或诱发释放会导致树突更大程度的延伸。相反，突触前释放位点密度的增加会导致树突范围的减小。这些生长调整在树突局部发生，是突触前位点附近神经突生长促进或抑制的结果。我们提供的证据表明蛋白激酶A的突触后活性状态在介导这种结构调整中起作用，这种结构调整会根据突触活性改变树突生长。这些发现表明，至少在连接的早期阶段，树突表现为一种稳态装置，会根据接收的输入水平和分布调整其大小和几何形状。因此，生长中的树突会抵消突触密度和活性的自然变化，以确保达到适当的输入水平。
